US EPA

4829244 

Journal Article 

Melt-based screening method with improved predictability regarding polymer selection for amorphous solid dispersions 

Auch, C; Harms, M; Mäder, K 

2018 

Yes 

European Journal of Pharmaceutical Sciences
ISSN: 0928-0987
EISSN: 1879-0720 

English 

30172803 

10.1016/j.ejps.2018.08.035 

The predictability of preformulation screening tools for polymer selection in amorphous solid dispersions (ASD) regarding supersaturation and precipitation was systematically examined. The API-polymer combinations were scaled up by means of hot-melt extrusion and spray-drying to verify the predictions. As there were discrepancies between a solvent-based screening and performance of ASD, a new screening tool with improved predictability at minimal investments of time and material is presented. The method refinement resulted in a better correlation between the screening and ASD prototypes. So far, a purely solvent-based screening was used which consisted of film casting by rapid solvent evaporation. This approach was improved by applying a heating step after film casting. Four representative polymers were tested with two different model active pharmaceutical ingredients (API) under non-sink dissolution conditions. Polyvinylpyrrolidone (PVP) based polymers showed no benefit towards pure API in the solvent-based screening but good supersaturation as ASD formulations. The extrudates with cellulose derivatives hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate phthalate (CAP) showed lower supersaturation than predicted by the solvent-based screening but performed especially well as spray-dried dispersions (SDD). False negative results for PVP-co-vinyl acetate (PVP-VA64) could be avoided by using the new melt-based screening. Furthermore, comparing the results from the two different screening methods allowed predicting the performance of extrudates vs. SDD with cellulose derivatives as polymeric excipients.